A Clinical Study Investigating the Safety, Tolerability, PK and PD of PCO371 in Patients With Hypoparathyroidism

NCT04209179 | Terminated Phase 1 FDA Drug

• 1 other identifier: PCO104UG
• Study Type: interventional
• Target: 5
• Locations: 3 countries
• Sites: 11

Brief Summary

This is a multi-center, placebo-controlled, randomized, double-blind, multiple-ascending dose study in patients with hypoparathyroidism. The total duration of study medication treatment will be 13 weeks and includes a Fixed-Dose Treatment period and a Dose Titration Treatment period. The Fixed-Dose Treatment period consists of multiple daily dosing at a fixed dose level. Once patients have completed the Fixed-Dose Treatment period, patients will enter the Dose Titration Treatment period where PCO371 (or placebo), oral calcium and oral active vitamin D can each be titrated according to the patient's albumin-corrected serum calcium level.

Conditions

Hypoparathyroidism

Outcome Measures

Primary Outcomes (7)

• Treatment-emergent adverse events

  Treatment-emergent adverse events (TEAEs) will be assessed including the number and rate of TEAEs.

  13 weeks

• Selected adverse events

  Hypercalcemia and hypocalcemia will be assessed including the number and rate of these.

  13 weeks

• Clinically significant change in the safety parameters; vital signs

  Abnormal change in vital signs.

  13 weeks

• Clinically significant change in the safety parameters; body weight

  Abnormal change in body weight.

  13 weeks

• Clinically significant change in the safety parameters; physical examination findings

  Abnormal change in physical examination findings.

  13 weeks

• Clinically significant change in the safety parameters; laboratory test value

  Abnormal change in laboratory test value including hematology, biochemistry, coagulation, urinalysis.

  13 weeks

• Clinically significant change in the safety parameters; electrocardiogram results

  Abnormal change in electrocardiogram results including PQ (PR), RR, QRS, QT, pulse, QTcB, QTcF and ECG abnormalities.

  13 weeks

Secondary Outcomes (9)

• Pharmacokinetic data of PCO371; Plasma concentrations of PCO371

  13 weeks

• Pharmacokinetic data of PCO371; AUC0-last

  13 weeks

• Pharmacokinetic data of PCO371; Cmax of PCO371

  13 weeks

• Pharmacokinetic data of PCO371; Tmax of PCO371

  13 weeks

• Pharmacokinetic data of PCO371; T1/2 of PCO371

  13 weeks

Study Arms (4)

PCO371 Low Dose and Low administration frequency

EXPERIMENTAL

PCO371 low dose and low administration frequency by oral administration for the first period ( Fixed-Dose treatment period). PCO371 will be titrated in the following period (Dose Titration Treatment period).

Drug: PCO371

PCO371 High Dose and Low administration frequency

EXPERIMENTAL

PCO371 high dose and low administration frequency by oral administration for the first period ( Fixed-Dose treatment period). PCO371 will be titrated in the following period (Dose Titration Treatment period).

Drug: PCO371

PCO371 High Dose and High administration frequency

EXPERIMENTAL

PCO371 high dose and high administration frequency by oral administration for the first period ( Fixed-Dose treatment period). PCO371 will be titrated in the following period (Dose Titration Treatment period).

Drug: PCO371

Placebo

PLACEBO COMPARATOR

Placebo by oral administration.

Drug: Placebo

Interventions

PCO371 DRUG

PCO371 capsule

PCO371 High Dose and High administration frequency; PCO371 High Dose and Low administration frequency; PCO371 Low Dose and Low administration frequency

Placebo DRUG

Placebo capsule

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide written informed consent, to use the device for PRO and electronic diary and to comply with the requirements of the protocol.
• Adult males or females ≥18 years of age
• History of hypoparathyroidism for more than 1-year post initial diagnosis
• PTH level is inappropriately low
• Dose of thyroid replacement therapy must have been stable for ≥3 months prior to first dose if receiving thyroid replacement therapy
• Receiving treatment with active vitamin D therapy (calcitriol ≥0.25 μg/day or alfacalcidol ≥0.5 μg/day)
• Receiving Oral calcium treatment (≥1000 mg/day)
• No significant changes in the diet from 4 weeks prior to Screening and for the duration of the study.
• Fasting albumin-corrected serum calcium concentration between 8.0 and 9.0 mg/dL at 2 consecutive visits during the Run-In period, and no more than 25% change in daily doses of oral Ca and active vitamin D between the 2 consecutive visits during the Run-In period.
• On Day 1, fasting albumin-corrected serum calcium level between 7.5 and 9.0 mg/dL
• Serum magnesium level ≥ lower limit of normal and ≤ 1.2 x laboratory upper limit of normal
• Serum 25\[OH\] vitamin D level within the laboratory normal range
• Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2
• Women of childbearing potential must have a negative highly sensitive urine or serum pregnancy test result
• For women of childbearing potential: agreement to use a highly effective contraceptive method during the treatment period and for 28 days after the last dose of study drug. Hormonal contraceptive methods must be supplemented by a barrier method (preferably male condom) and agreement to refrain from egg donation during the treatment period and for 28 days after the last dose of study drug.

You may not qualify if:

• Pregnant or breastfeeding or intending to become pregnant during the study or within 28 days after the last dose of PCO371
• Known or suspected history of hypoparathyroidism resulting from an activating mutation in the Ca-sensing receptor gene or impaired responsiveness to PTH (pseudohypoparathyroidism)
• Clinically significant hypomagnesemia. Adequately treated hypomagnesemia is permitted
• Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism
• History of a major bone fracture within 3 months prior to Screening
• Any history of clinically significant bleeding disorder or clinically significant abnormal clotting times
• History of thyroid cancer unless documented to be disease free for ≥1 year
• History of any other cancer in the past 3 years from Screening with the exception of thyroid cancer , completely removed nonmelanoma skin cancer, basal cell skin carcinoma, and cancer in situ of the cervix
• Dependence on monthly or more frequent parenteral calcium infusions to maintain calcium homeostasis
• Disease processes that may adversely affect gastrointestinal absorption
• Use of oral bisphosphonates within 6 months of Screening and/or intravenous bisphosphonate preparations within 12 months of Screening. Any use of zoledronic acid prior to Screening.
• Use of other drugs known to influence calcium and bone metabolism such as calcitonin, fluoride tablets or cinacalcet hydrochloride within 4 weeks prior to Screening.
• Patients who have taken inducers of CYP3A4, Pgp,or BCRP within 1 month before IMP administration or taken inhibitors of CYP3A4, P-gp, or BCRP within 2 weeks before IMP administration (or either 6 times the t1/2 of the drugs mentioned above, whichever is longer).
• Use of loop or thiazide diuretics within 14 days prior to first dose of IMP
• Use of anti-coagulants, anti-platelet medications, and aspirin within 2 weeks (or within 6 times the t1/2 of the drug mentioned above, whichever is longer) prior to IMP administration

Sponsors & Collaborators

• Chugai Pharmaceutical: lead

Study Sites (11)

The Lundquist Institute

Torrance, California, 90502, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Endocrinologie et néphrologie Centre de recherche du CHU de Québec

Québec, CAN, G1V 4G2, Canada

Location

McMaster University Bone Research & Education Centre

Oakville, Ontario, L6M 1M1, Canada

Location

Semmelweis Egyetem, Általános Orvostudományi Kar, Belgyógyászati és Onkológiai Klinika

Budapest, HU, 1083, Hungary

Location

MeSH Terms

Conditions

Hypoparathyroidism

Interventions

PCO371

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases

Study Officials

• Sponsor Chugai Pharmaceutical Co. Ltd

  clinical-trials@chugai-pharm.co.jp

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2019
• First Posted: December 24, 2019
• Study Start: July 23, 2020
• Primary Completion: December 28, 2020
• Study Completion: May 25, 2021
• Last Updated: June 11, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share

Locations

CA (2); US (8); HU (1)